This research project is designed to explore the concept that the mechanisms which regulate rapid eye movement (REM) and slow wave sleep (SWS) are modified in depressed individuals. Some of the abnormalities observed in the REM and NREM sleep of depressives appear to be "episodic" and most often occur only during depressive episodes, whereas others are more "persistent" and remain visible during well intervals. The sources of these abnormalities in the sleep EEG are unknown. We would suggest, however, that they involve such factors as genetic predisposition, chronophysiological mechanism, and the course of the illness itself and the interaction of course with aging and with both acute and maintenance antidepressant therapies. The proposed studies aim to evaluate empirically the effects of these factors on REM and SWS in depressives and to explore the impact of these factors on sleep regulation in normals. The following experimental goals are proposed: 1) to study intensively the evolution of antidepressant response and develop the capacity to identify the EEG sleep correlates of acute antidepressant response. We will pursue an expansion of our pulse-loading dose strategies with clorimipramine in acutely depressed in patients. Because of this agent's relatively long pharmacokinetic half-life, pharmacodynamic counter-clockwise hysteresis and potent suppression of serotonin reuptake, this strategy will provide an opportunity to examine the unfolding of antidepressant action on sleep EEG and clinical state; 2) To probe the REM and SWS systems with partial sleep deprivation in order to magnify and/or unmask underlying sleep EEG abnormalities in depressed patients during clinical recovery; 3) To continue the development of new methods of sleep EEG analysis in order to characterize specific critical parameters in the sleep of normals and depressed patients; 4) To evaluate the effects of age and sex on sleep architecture in well-screened normal subjects, studied both longitudinally and cross-sectionally; 5) To examine specific change sin REM and SWS as they unfold over the course of illness, recovery, and recurrence in the same patients; 6) To evaluate further the contribution of familial factors in the manifestation of various EEG sleep abnormalities in normals, depressed individuals, and their first-degree relatives.